Dual functional peptide from olive flounder exerts antihypertensive and anti-muscle atrophy effects in spontaneously hypertensive rats

This study builds on previous research on bioactive peptides from Paralichthys olivaceus ( P. olivaceus ), focusing on a tripeptide (POIER) in Protamex-Pepsin assisted hydrolysate from P. olivaceus (POppH). The blood pressure-lowering effects of POIER were confirmed in vitro and in vivo studies. In the present study, the in vivo antihypertensive efficacy of POppH and its potential anti-muscle atrophy activity were investigated. In an in vivo spontaneously hypertensive rat (SHR) model, POppH administration reduced blood pressure and alleviated aortic and cardiac fibrosis. In an in vitro dexamethasone (Dexa)-induced C2C12 myotube model, both POppH and POIER enhanced myoblast proliferation, differentiation, and myotube formation through upregulation of MyHC, MyoD, myogenin, p-mTOR, and p-Akt, while downregulating muscle degradation markers such as FoxO3a, MuRF-1, and MAFbx. Molecular docking analysis indicated that POIER interacts with the mTOR active site and may inhibit angiotensin II binding to angiotensin II type 1 receptor (AT1R). These results highlight the dual functionality of POppH and POIER in supporting cardiovascular and muscular health. Graphical abstract • POppH regulate systolic and diastolic blood pressures in SHR. • POppH improve hypertension induced muscle loss and muscle strengthening effects in SHRs. • POIER activates the PI3K/AKT/mTOR pathway and suppresses muscle degradation mediators. • POIER promotes myoblast proliferation and myotube formation in C2C12 cells. • Molecular docking suggests POIER interacts with mTOR and inhibits Ang II at AT1R.